Severe Leptospirosis & AKI : A Report of 2 Cases from Bermuda

Leptospirosis is a  globally-transmitted zoonosis due to infection with Leptospira spp.,a motile, obligate aerobic, spiral bacteria from contaminated soil, water or rat urine. The clinical presentation of infection may be protean. We present two cases of severe AKI and hyperbilirubinemia with severe sepsis, due to leptospiral infection in Hamilton, Bermuda. In many cases, the disease may be mild, but severe cases with fever, AKI and jaundice (Weil's disease)  require prompt diagnosis  and therapy . In many cases the diagnosis may be delayed. The aim of this report is to show how rapid diagnosis can impact survival in severe cases of Leptospirosis with severe AKI, jaundice and other organ involvement. We also provide an algorithm to facilitate rapid diagnosis

Retrospective review of 2 cases of AKI with Leptospirosis. Case #1. A 72-year-old gardener presented to hospital with fever, muscle aches and nausea. Physical examination revealed jaundice, tachycardia  of 106/min, BP 110/86mmHg, and hepatosplenomegaly. Labs showed BUN of 53, serum creatinine of 5.1, bilirubin 12mg/dl (conjugated), thrombocytopenia of 20,000, with 2+ proteinuria on urinalysis,10-15rbc/hpf. Leptospira IgM  Antibodies were + Microscopic Agglutination (MAT) & ELISA..  Tests for Hepatitis B antigens and Hepatitis C antibody & HIV assays were negative. The rest of lab data are shown in Table 1. Renal failure progressed as shown in figure 1, but dialysis was not done. Ceftazidme & Doxycycline were given for  2 weeks and supportive care led to improvement to discharge. Patient had residual kidney disease on discharge and now has CKD stage 3.

Case # 2: A 70 year-old , homeless man presented to hospital with leg pain, myalgias, nausea, weakness and fever of 101F. Physical exam showed encephalopathy, tachycardia and hepatosplenomegaly. In the ER, BP was 126/73, Pulse 96/min Pulse ox 96% saturation. He  had a seizure, and BUN was 168mg/dl, Serum creatinine was 14.5, CPK 16,000, Liver enzymes were markedly elevated. Bilirubin was  21mg/dl. Urgent hemodialysis was done for severe Uremia. Leptospira IgM antibody was positive by Microscopic Agglutination(MAT) .  After 4 dialysis sessions, and IV Cetriaxone & Doxycycline, renal function recovered as shown in Figure 1.Hyperbilirubinemia also steadily cleared. Labs & evolution of AKI are shown in Tables 1 & Figure 1.

Table 1. Admission Parameters of 2 Cases of Leptospirosis

     Both patients presented with severe AKI, hyperbilirubinemia, sepsis and hepatitis with transaminitis. The differential diagnosis of this presentation includes acute viral hepatitis, drug toxicity, severe malaria, hepato-renal syndromes,  septic shock with ischemic hepatitis, or  bile cast nephropathy. Quick diagnosis of probable Leptospirosis was enhanced by high index of suspicion and rapid laboratory confirmation with MAT test & ELISA. Rapid institution of beta lactam antibiotics( Ceftazidime & Ceftriaxone) and Doxycycline, along with supportive care in intensive unit led to good outcomes in both cases. The second patient required 4 sessions of hemodialysis, but made complete recovery. Case #1 had residual chronic kidney disease (CKD stage 3). The presentation of clinical leptospirosis infection is highly variable, and there is a tendency to delayed diagnosis, especially if the index of suspicion is low.[1]  Very mild cases are likely to be missed. Severe cases with AKI and severe jaundice (Weil's disease) require prompt diagnosis to save lives.[2]. Our case series is unique because diagnosis was made early and treatment ( antibiotics) were  started before confirmation of diagnosis, as recently recommended.[2] The combination of AKI & conjugated hyperbilirubinemia, should raise  a strong suspicion of this diagnosis, especially in areas with rat infestation. Use of rapid diagnostic tests and MAT would clinch the diagnosis. In both our cases, rapid tests, ELISA -based IgM antibody tests were obtained while waiting for MAT(gold standard), enabling rapid diagnosis, aggressive IV fluids, nursing care, isolation precautions( highly contagious) fever control and rapid institution of antibiotics. These played critical roles in our successful outcome with renal recovery. The  US CDC reports about 100-150 cases annually with variable mortality[3], likely related to late diagnosis. AKI appears to result from combination of acute tubular necrosis(ATN) and acute tubulointerstitial nephritis (AIN). Steroids may be useful if there is evidence of vasculitis. Our patients recovered without steroids

In conclusion, leptospirosis must be considered in the differential diagnosis of AKI, jaundice ( conjugated hyperbilirubinemia) and sepsis with variable organ failure. Empiric antibiotics, aggressive fluid resuscitation must be initiated, as well as rapid diagnostic tests while awaiting MAT results.  We document the clinical course of 2 cases of leptospirosis in Bermuda, with good outcome.

References:

1. Cetin BD, Harmankaya O, Gunduz A, Oktar M, Seber E. Acute renal Failure : a common manifestation of leptospirosis. Ren Fail 2004;26:655-661

2.Sibel YC, Aysegul K, Arzu K. Murvet Y, Suheyla A. Leptospirosis with Acute Renal Failure and Vasculitis. A Case Report. 

3. Monthly Communicable Disease Report. Sandiego County, 2024; Vol 8, Issue 2, Page 1.